INFLAMMATION AND REPAIR

Inflammation:
i) Cardinal signs of inflammation
ii) Inflammatory process
a) Vascular events
b) Cellular events
iii) Chemical mediators of inflammation
a) Plasma protein
b) Cell associated/products of cell
iv) Cells of inflammation and their function
v) Types of inflammation
vi) Process of healing
Definition of inflammation:
i) Inflammation is the reaction of tissue to an irritant.
ii) Inflammation is a dynamic process which begins following sublethal injury to tissues
and usually ends with complete healing.
Irritants/injurious agents of inflammation:
i) Pathogenic microorganisms or their products, eg. bacteria, virus, protozoa, bacterial
toxins etc.
ii) Chemical agents eg. organic and inorganic poisons
iii) Mechanical or thermal injury eg. injury due to heat, cold, trauma etc.
iv) Immunologic reaction

1. Cardinal signs of inflammation:

rubor et tumor cum calor et dolor, functio laesa.

redness and swelling with heat and pain, loss of function.

Inflammation is a beneficial phenomenon, explain.

In acute inflammation, the following events occurs-
i) Redness – is due to increased blood supply
ii) Swelling  is due to exudation of serum fluid
Effects of (i) + (ii)
a) Increased blood & serum bring more O2 for metabolism
b) It brings more nutrients for injured tissue
c) The serum fluid will dilute and drain away the irritant
d) Antibodies and reactive cells are brought
(iii) Heat  is due to increased blood supply
Effect of (iii)
a) It increases the enzymatic activity to some extent in certain limit.
b) It destroys some heat labile toxins.
iv) Pain- is due to the pressure of exudates on the nerve endings. Chemical mediators,
injurious agents may also induce pain.
Effect:
a) It awares the animal about inflammation.
b) It incites some reflex which inhibits the muscular movement in that particular area
for healing.
v) Loss of functions due to inhibition of muscular movement (Pain reflex)
- is due to tissue destruction
- is due to mechanical (swelling)
Effect:
It gives chance to recover quickly
Conclusion: From the above points, it is clear that inflammation is a protective
mechanism and no animal can survive without inflammation. So, inflammation is a
beneficial phenomenon.
Occasionally, inflammation may prove to harmful in
i) Fibrous scar formation in liver (cirrhosis)
ii) Hypersensitivity  excessive reactions which were not required
2. Inflammatory process:
It is the interplay of at least 4 major components
A) Vascular endothelium
B) Leukocytes and platelets
C) Other fixed cells (mast cells, MQ, fibroblast etc.)
D) Chemical mediators
a) Plasma protein
b) Cell products
a) Vascular events of inflammation: Events that take place in blood vessels.
Changes that occur in the blood vessel
(i) Transient constriction of blood vessels It is due to damaging stimuli of irritant. It is
mediated by axon reflex resulting in constriction of arteriolar smooth muscle.
(ii) Vasodilation: It is due to second nervous reflex, chemical mediators.
Effects of vasodilatation:
a) Acceleration of blood flow
b) Retardation of blood flow (stasis of blood)
c) Increase capillary hydrostatic pressure
d) Disruption of laminar flow
(iii) Increased vascular permeability: It is due to some chemical mediators. There are 3
patterns of increased permeability
 Immediate transient response
 Immediate sustained response
 Delayed prolonged response
Effect: The ultimate important consequence of vascular change is exudation. The
functions of exudation are as follows:
 Dilution and drainage of irritants
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  Brings plasma protein
 Brings antibodies, reactive cells (actively come)
Categories of endothelial lining:
i) Continuous endothelium: Widely distributed in most tissue. There may be gap junction.
ii) Fenestrated endothelium: There may be discontinuation in the endothelial cells. Some
endothelial cells are missing or reduced to only membrane at some places. Basement
membrane is complete, eg. glands, glomerulus, intestinal mucosa.

iii) Sinusoidal endothelium: The endothelial cells have pore in it. The underlying
basement membrane is incomplete or entirely absent, eg. liver, spleen.
iv) High endothelium: Specialized endothelium, slightly columnar. They regulate the
movement of the lymphocytes. They are present in post capillary venules of lymphoid organ.
HP OP Interstitium
Arteriole  30 mmHg 28 mmHg HP = 5.3 mm Hg Negative
Capillary  17 mmHg 28 mmHg OP = 6mm Hg
Venule  10 mmHg 28 mmHg Hence,
Resultant = 6-(-5.3) mm Hg
= 11.3mm Hg toward intersitium

Normal fluid exchange

Arteriole Capillary Venule
HP = 30 mmHg 17 mmHg 10 mmHg

OP = 28 mmHg 28 mmHg 28 mmHg

2mmHg 11mmHg 18mmHg

11.3mmHg 11.3mmHg 11.3mmHg
Arteriolar side:
Resultant = 2 + 11.3 = 13.3 mmHg toward interstitium
Capillary side:
11.3  11 = 0.3 mmHg toward the interstitium
Venular side:
Resultant = 18  11.3 = 6.7 mmHg toward the capillary
So, at the ateriolar end fluid enter the interstitium from vessel and in venular end the
fluid enter the vessel from interstitium.
b) Cellular events in inflammation:
It takes place in 4 stages
i) Margination of the leukocytes along the vessel wall
ii) Adhesion of the leukocytes to vessel wall
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iii) Emigration of leukocytes from the vessels
iv) Chemotaxis of leukocytes
Short description:
i) Margination of leukocytes along the vessel wall:
a) Retardation of blood flow or stasis of blood flow causes the disruption of laminar flow
b) The cells come close to the vessel wall
ii) Adhesion of leukocytes to vessel wall:
Leukocytes adhere with vessel wall due to
a) Leukocytes are sticky in nature
b) Some chemical mediators induce the synthesis of some adhesion molecules on the
surface of both endothelial cells and leukocytes
3 types of adhesion molecules are
a) Immunoglobulin super family: eg. Intercellular adhesion molecules (ICAM) and
vascular cellular adhesion molecules (VCAM). Both are attached to the surface of the
endothelial cells.
b) Integrin family: eg. 1 & 2 integrins are expressed on the surface of the lymphocytes.
c) Selectin family: eg. E-selectin and P-selectin. They are expressed on endothelial cell surface.
(iii) Emigration of leukocytes from the vessels:
Leukocytes migrate actively across the blood vessel but erythrocytes passively. Adhered
molecules form pseudopodia and squeeze through endothelial junction.
iv) Chemotaxis of leukocytes:
Chemotaxis is the movement of a cell along the increasing gradient of concentration of chemical
attractant (chemotactic molecule). It is of two types -positive and negative chemotaxis.
Chemotactic molecules in inflammation:
 Soluble bacterial product- Bacteria can attract neutrophil by chemotaxis
 Complement component – eg, C5a C567,They are highly chemotactic
 Leukotriene – The products of leukocytes
 Various cytokines
3. Chemical mediators of inflammation.
3. a) Plasma enzyme systems- There are 4 enzyme system
i) The coagulation cascade
ii) The kinin system
iii) Fibrinolytic system
iv) The complement cascade
(i) Coagulation cascade:
Intrinsc pathway Extrinsic pathway
Hageman factor Tissue thromboplastin
Kallikreins MQ
Plasmin Endothelial cells
Surface contact Fibroblast
Activated Hageman factor (XIIa)

Prothrombin Thrombin

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Fibrinogen Fibrin
Function of fibrin in inflammation:
 It provides a matrix for the chemotactic migration of leukocytes and phagocytosis by
leukocytes
 It provides a limited barrier to motile microorganisms
(ii) The Kinin system:
Activated Hageman factor (XIIa)

Prekallikrein Kallikrein (enzyme)

High molecular
weight kininogen Kinin (Bradykinin)
Functions:
 Bradykinin causes vasodilation and increases vascular permeability
 Bradykinin activates phospholipase-A2 to initiate the production of prostaglandins
and leukotrienes
 Bradykinin is responsible for the induction of pain
 Kallikrein can also convert complement component C 5 to C5a, a very potent chemical
mediator
 Prekallikrein and high molecular weight of kininogen can further activate the
Hageman factor
(iii) Fibrinolytic system:
Activated Hageman factor (XIIa)

Plasminogen activator Inassociation with prekallikrein and HMW kininogen

Plasminogen Plasmin

Fibrin Fibrin split products (soluble)

Functions:
 Plasmin degrades fibrin to fibrin split products which are soluble and removed via
lymphatics
 Fibrin split products are chemotactic for neutrophils
 Plasmin can also activate Hageman factor
 Plasmin can convert C3 complement to C3a and C3b
 Plasmin can also convert kininogen to kinin
(iv) Complement cascade:
The complement system consists of at least 9 groups of plasma protein which are once
activated undergo a cascade reaction and the end product is a membrane attack complex
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(MAC) which cause complement mediated lysis of bacteria, parasite, foreign cells, virus
infected cells etc.
Functions:
 C2 causes vasodilation and increases vascular permeability
 C3a, C4a & C5a are anaphylaxin and release histamine by mast cell degranulation &
cause vasodilation, increases vascular permeability and smooth muscle contraction
 C5a is a chemotactic factor
 C3a can act as opsonin (a protein which can coat antigen and the neutrophil can engulf
the antigen easily)
3.b) Cell associated chemical mediators:
Cell associated chemical mediators are
i) Cytokines
ii) Arachidonic acid metabolites
iii) Platelet activating factor
iv) Vasoactive amines
v) Other granular constituents of cells
vi) Oxidising reagents
(i) Cytokines: They play a crucial role in immune response, inflammatory response and
haematopoiesis.
Cytokines having inflammatory roles are-
a) Interleukin-1: Produced mostly by Macrophage but also be produced by
endothelial cells & fibroblast
b) Tumor necrosis factor (TNF-)- It is also called cachectin and produced by MQ & mast cell
c) Interferon (IFN)- Produced from lymphocytes
Function:
On endothelial cells
i) Acts on endothelial cells, expression of adhesion molecule
ii) Production of thromboplastin
iii) Decreased production of thrombomodulin.
On leukocytes
i) Expression of adhesion molecules
ii) Activation and proliferation
iii) Activation of phospholipase-A2
On fibroblast
i) Proliferation and increase collagen synthesis
Systemic function
i) Fever
ii) Synthesis of acute phase protein
iii) Change in heavy metal concentration in plasma
iv) Increase muscle catabolism
v) Leukocytosis
II) Arachidonic acid metabolites:
It includes
- Prostaglandins
- Leukotrienes
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 - Thromboxane & also
- lipoxin
Arachidonic acid in cell membrane.

Corticosteroid Phospholipase-A2

Arachidonic acid in cell cytoplasm

cycloxygenase lipoxygenase
pathway pathway

Prostaglandin Leukotrienes
and thromboxane and lipoxin
aspirin and ibuprofen acts
on and block the enzymatic
activity to produce prostaglandin
and reduce inflammation.

Function:
- Vasodilation & increased vascular permeability
- Smooth muscle contraction
- Increased leukocytic activity
- Induction of pain
- Platelet aggregation
- Vasoconstriction
III) Platelet activating factor: It is also called acetyl-glycerol-ether-phosphoryl choline
(AGEPC) which is produced by neutrophil, monocytes, basophil, macrophages, mast
cells, endothelial cells and in some cases platelets.
Function:
- Platelet aggregation
- Vasodilation
- Increased vascular permeability
- Chemotaxis and stimulation of granulocyte
IV) Vasoactive amines: They are histamine and serotonin. Histamine is produced from
mast cell, basophils, occasionally in eosinophil and platelet and serotonin from mast cell
and platelet.
Function:
- Vasodilation & increases vascular permeability
- Smooth muscle contraction
- Increases mucus secretion
V) Other granular constituent of leukocytes:
In mast cell
-Protease enzyme- digests basement membrane of blood vessel
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 -Heparin-Anticoagulant
-Chemotactic factor
In granulocytes & macrosphages
-Lysosomal granule contains protease enzyme which cause damage of tissue and
increase the severity of inflammation
VI) Oxidizing reagent: These are free radicals which are released by neutrophils. They
cause damage of tissue and enhance the severity of inflammation.
4) Cells of inflammation:
The cells are
i) Neutrophil
ii) Eosinophil
iii) Basophil & mast cell
iv) Monocyte & Macrophage
v) Lymphocytes
Description in short
(i) Neutrophils:
Synonyms: Pus cell, polymorph nuclear cell, microphage, heterophil in bird, rabbit & guinea pig.
Morphology: Numerous and fine granule in cytoplasm. The nucleus is lobulated (3-5 lobes).
Granules:
i) Azurophil granules- myeloperoxidase enzyme
ii) Neutrophil specific granule- hydrolase, protease, lysozyme
Origin: Bone marrow
Life span: 6 hours
Pseudoeosinophil: Bird’s neutrophil is reddish and hence called so.

Function:
- Phagocytosis
- Kill and digest engulfed cell
- Release chemical mediators of inflammation
- Release tissue degradative enzyme and free radicals
Two process of phagocytosis
i) Surface phagocytosis- engulf foreign particle held against surface
ii) Phagocytosis after opsonization
Opsonization: Coating of antigen/microorganism with some protein and this protein is
called opsonin C3b.
II) Eosinophil:
Morphology: - Lobulated nucleus (2-3 lobes)
- Eosinophilic coarse granule in cytoplasm
- Size and shape varies species to species
Origin: Bone marrow
Number: Very low (1-8%)
Function:
- Limited phagocytosis
- Cytotoxicity to non-phagocytable target (parasite)

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 - Enhance the inflammatory process by damaging tissue

III) Basophils and mast cells:

Morphology: Size and shape varies within and between species
- Nucleus is large and oval with large nucleolus
- Spherical basophilic and metachromatic granules in cytoplasm over sheds the nucleus
- End stage cells
- Basophilic i.e. bluish
Origin: Bone marrow
Number: Basophil is very low in circulation (up to 1%) but mast cells are abundant in
tissue (skin, respiratory mucosa, GI mucosa).
Stimuli for degranulation of mast cell:
- Cross linking of surface immunoglobulin E (IgE) with appropriate antigen
- Complement component (C3a, C4a, C5a, etc.)
- Physical stimuli (trauma, cold, light)
- Substance ‘p’ from nerve endings
NB: Toludine blue is special stain of mast cell
Function:
 Release of histamine and serotonin
 Release of heparin
 Synthesis and release of leukotrienes
 Production of tumor necrosis factor (TNF- )
IV) Monocytes and other macrophages
Synonyms: Mononuclear cells, mononuclear phagocytes
Types of macrophage:
a) Wandering macrophages
b) Fixed macrophages
 Von küpffer cells in liver
 Alveolar macrophage (dust cell) in lung
 Pleural and peritoneal macrophage
 Fixed macrophage in lymphoid organ
 Fixed macrophages in mucosal tissue
 Histiocytes in connective tissue
 Glial cell in CNS
 Osteoclast in bone
Morphology:
 Indented nucleus
 Relatively abundant cytoplasm
 Tissue macrophages are relatively larger, irregular shape and also volumenous
cytoplasm often with multiple vesicular granules
Function:
 Phagocytosis of foreign bodies
 Processing and presentation of antigens to lymphocytes
 Secretion of inflammatory mediators

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  Interleukin-1
 Tumor necrosis factor (TNF-)
 Platelet activating factor
 Prostaglandins
 Secretes some coagulation factor: V, VII, thromboplastin

 Liberation of enzymes which cause tissue damage enhancing inflammation

 Helps in healing process

 Clear up the tissue debris which is prerequisite of healing

 Stimulate blood vessel formation, proliferation of fibrous connective
tissue & collagen synthesis
 Stimulates the production of granulocytes and also monocyte

N.B. Giant cell: Several macrophages fused to form giant cell

Types of giant cells
i) Langhans type
ii) Touton type
iii) Foreign body type
iv) Reed sternburgh giant cell- found in malignant lymphoma (Hodgekin type)
v) Lymphocytes:
Morphology:
 Compact nucleus
 Scanty cytoplasm
Plasma cell: derives from B-lymphocyte
 Spherical or elliptical with eccentric nucleus which is cart wheel appearance
 Cytoplasm may contain hyaline sphere which are called “Russel body”
 Cytoplasm is slightly eosinophilic and slightly magenta or purplish shade
Function in relation to inflammation
- B-lymphocytes are differentiated to plasma cell and produce antibody to induce
humoral immune (HI) response
- T- Lymphocytes are involved in cell mediated immune (CMI) response
VI) Other cells:
- Endothelial cells are involved in inflammatory response
- Fibroblasts are involved in healing process
5. Types of inflammation
Types of inflammation depends on the following factors
- Anatomical site of inflammation
- Inflammatory stimuli
- Immunocompetence of the host
A) In general, inflammation can be divided into
a) Acute inflammation
b) Chronic inflammation

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Difference between acute and chronic inflammation:
Acute inflammation Chronic inflammation
(i) Arise suddenly often within minutes (i) Arise slowly
or hours
(ii) Progress very rapidly (ii) Progress slowly
(iii) Lasts for few hours to few days (iii) Lasts for weeks, months or years
(iv) Exudative (iv) Mainly proliferative and productive

B) Classification of inflammation on the basis of exudate and reactive cells:

i) Serous inflammation
ii) Fibrinous inflammation
iii) Purulent inflammation acute inflammation
iv) Haemorrhagic inflammation
v) Catarrhal inflammation
vi) Granulomatous inflammation chronic inflammation
vii) Other chronic inflammation

Description of acute inflammation:

i) Serous inflammation: It is characterized by the exudate containing serous fluid. It is
called inflammatory oedema.
Occurrence: Mostly in
a) Serous sac
b) Lungs, epidermis, mucosa, joint cavity etc.
Causes:
- Usually by mild irritant
- Early stage of bacterial/viral infection
- Inhaled chemicals
- ANTU (Alpha napthyl thiourea) - a rat poison which after ingestion is excreted by
lungs
- Second degree burn
- Some viral disease eg. FMD, vesicular stomatitis (inflammation in the oral cavity)
- Traumatic injury to synovial joints
Gross appearance:
Clear or cloudy straw coloured fluid in the body cavity (pleura, peritoneum, pericardium,
joint cavities, natural or artificial tissue spaces. The fluid is more cloudy (specific gravity
> 1.017).
Microscopic characters:
- Homogenous pink coloured protenaceous mass in the distended natural or artificial
tissue space
- Few leukocytes

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 - Trace amount fibrin
- Hyperemia and congestion of nearby blood vessels
Significance & outcome
- Dilute irritant
- Bring antibody
- Sometimes relief pain by lubricating the irritated surface
II) Fibrinous inflammation: It is characterized by exudate containing fibrin.
Occurrence: Mostly in mucous membrane, serous membrane and also in lungs.
Causes: It is caused by certain microorganism of relatively high virulence
- Corynebacterium diphtheriae
- Pasteurella multocida- Haemorhagic septicemia in cattle
- Spherophorus necrophorus- calf diphtheria
- Rinder pest & PPR viruses
- Avian laryngotracheitis viruses
-Avian mycoplasmosis
- Feline infectious peritonitis virus
Gross appearance:
- Initially a dull or cloudy haze on the surface (early stage of fibrinous inflammation)
- Whitish stringy materials covering a surface or hanging from surface
- Formation of pseudomembrane
- Underlying tissue may be hyperemic & necrotic
The membranes are of two types
i) Diphtheritic membrane: Thin and firmly attached
ii) Croupous membrane/fibrinous cast: Volumenous, loosely attached, molded to the
shed of vessel which may come out as a cast
Microscopic appearance:
- Pink coloured network of fibrin (in lung)
- Associated with leukocytes
- Coagulation necrosis and hyperemia/congestion in underlying tissue
Significance and outcome:
- Protects underlying tissue from irritant
- Prevent blood loss from irritant
- Soothing effect of fibrin
If the cause is withdrawn the ultimate effect is fibrinolysis and regeneration of damaged
tissue otherwise the fibrinous exudate will undergo organization (formation of fibrous
tissue). It causes adhesion of two opposing surface (carnification).
III) Purulent inflammation: The purulent inflammation is characterized by the exudate
containing pus.
N.B. Pus contains
- Living or necrotic neutrophil
- Necrotic cells of preexisting tissue
- Serum
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 - Bacteria may also be present

Occurrence:
- May occur in any part of the body including bone but mainly occur in kidney.
Causes:
It is usually caused by pyogenic bacteria
- Staphyllococcus spp.
- Streptococcus spp.
- Corynebacterium spp.
- Esherichia coli (occasionally)
- Bacillus tuberculosis (early stage)
Gross appearance:
- Viscous cream coloured fluid, semisolid, watery to almost solid
- Occasionally red discolouration of pus due to haemorrhage
- Greenish discolouration due to Pseudomonas aeruginosa bacteria
Microscopic appearance:
- Considerable number of neutrophils
- May be associated with other cells like lymphocytes, plasma cells, macrophage etc.
- Hyperemia and congestion
- Small amount of fibrin or serum fluid
- May or may not be associated with liquefactive necrosis
Significance & outcome:
Most favourable outcome of purulent inflammation is liquefaction and drainage via the
lymphatics. Sometimes it may be encapsulated. Abscess may be metastasized. Other
outcome is sepsis and septicemia.
NB: Abscess
-Circumscribed collection of pus in tissues
- May have a capsule
- Size may vary from microscopic to unlimited size
Suppuration: Considerable amount of pus running from a surface or filling a natural
body cavity.
Phlegmon/Cellulitis: Small amount of pus in subcutaneous tissue in scattered form.
IV) Haemorrhagic inflammation: Haemorrhagic inflammation is characterized by
exudate containing blood.
Occurrence:
May occur in any parts of the body but common in mucous membrane and lungs.
Causes:
 Diseases caused by highly virulent microorganisms.
- Anthrax
- Black quarter
- Haemorrhagic septicemia
- Infectious laryngotracheitis
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 Acute poisoning with phenol, arsenic, phosphorus etc. which cause inflammation in
GI tract
Gross appearance:
- Blood mixed material which can be fluid or semisolid and usually clotted and
gelatinous
- Colour is not like pure clotted blood, rather variable
- Streaked on the surface
Microscopic appearance:
Diffusely distributed erythrocytes along with other component of blood like leukocytes
and fibrin which are present in a proportion higher than normal.
Significance & outcome:
- No definite significance
- Outcome usually leads to quick fatality
- If cause is withdrawn, inflammation subsides with equal rapidity
V) Catarrhal inflammation: This type of inflammation is characterized by exudate
containing mucus.
Occurrence: Occurs only in the mucous membrane
Causes:
- Irritants which are mild in nature or of short duration
- Bacteria or virus of low virulence
- Amoebic dysentery
- Irritating food (spicy food)
- Inhaled dust
- Inhaled gas eg. formalin, chlorine, chloropicrin etc.
Significance and outcome:
- Flow of mucus is protective
- If the cause is withdrawn, the flow subsides
Description of chronic inflammation:
i) Granulomatous inflammation: It is characterized by the formation of granuloma.
(Granuloma-closely packed collection of predominantly macrophages).
Occurrence:
- Occurs in any organ
Causes:
On the basis of cause it is of two type
a) Hypersensitivity type- Immune mediated granulomatous inflammation
b) Foreign body type
Hypersensitivity type:
- Intracellular microorganism- Mycobacterium, Brucella
- Some fungi
- Helminth and their ova (Schistosome)
- Autoimmunity to any cellular antigen
b) Foreign body type:
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 - Immunologically inert and nontoxic foreign body in tissue, eg. silk structure, oil
droplets, barium sulphate, bullet, wood splinter etc.
Gross appearance:
Single or multiple hard nodular swelling
Microscopic appearance:
- Closely packed collection of macrophages
-High turn over of MQ – hypersensitivity type
-Low turn over of MQ – foreign body type
- Associated with reactive cells- lymphocytes (hypersensitivity type)
- Epithelial cells-highly differentiated MQ with vesicular nodular nucleus and
indistinct cell outline
- Giant cells
- Proliferation of fibroblast and epithelial cells
Significance and outcome:
- Usually progressive in nature and often continues even after removal of causal agent
- Rarely granulomatous inflammatory reaction may be modulated to other acute type of
inflammation due to secondary infection or other modulated factor
VII) Other chronic inflammation:
They are not granulomatous in nature. A follow up of a long term or persistent acute
inflammation, particularly when the cause is not withdrawn or there is repeated exposure.
6. HEALING:
Healing is a process of restoring of an injured tissue as nearly as possible to its previous
normal size. Healing may occur in two ways
a) Healing by regeneration
b) Healing by repair
Regeneration: It is the process by which lost cells and tissues are replaced by the cells
or tissues of same kind.
Prerequisites of regeneration:
i) Tissue damage has to be limited
ii) Complete resolution, i.e. removal at all exudate and tissue debris
iii) Ability of the cells to regenerate
On the basis of ability of the cells to regenerate, the cells can be divided into three groups
(1) Labile cells: They multiply throughout the life and can easily regenerate. e.g. The cells of
epidermis, mucous membrane, uterine endometrium, bone marrow, lymphoid tissue etc.
(2) Stable cells: They do not normally multiply in a full grown body, but can do so if required
e.g. hepatocytes, renal tubular epithelium, cells of pancreas, thyroid, adrenal cortex etc.
(3) Permanent cells: These cells loss their ability of mitosis at about the time of birth.
They can not regenerate e.g. neuron, striated muscles etc.
Repair: It is the process by which damaged tissue is replaced by the proliferation of
fibrous connective tissue leading to the formation of scar.

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Process of repair:
It is a complicated process
- Clotting of exudate (formation of fibrin network)
- Invasion by macrophages
- Phagocytosis of dead cells & tissue debris
- Formation and anastomoses of new blood vessels from the periphery
- Proliferation of fibroblast from the periphery
- Synthesis of collagen by fibroblast
- Destruction of blood vessels by collagen
- Scar formation (avascular white CT)

F. Granulation of tissue:
It is newly formed highly vascular tissue found in the repair process which consists of
freshly grown fibroblast and perpendicular loops of capillaries.
Factors affecting the healing process:
- Absence of apposition
- Presence of infection
- Lack of blood supply
- Vit-C deficiency (collagen synthesis is affected)
- Sulphur containing amino acid deficiency
- Administration of glucocorticoides (It prevents the formation of new blood vessel)

Fever: Fever is the general functional response of body to an injury and it is commonly
associated with inflammation.

Pyrogens: The agents which can induce fever

e.g.
- Bacteria
- Breakdown product of tissue (collagen, matrix substance)
- Chemical mediators (Interleukin-1, prostaglandin, leukotrienes etc.)
How fever occurs: Pyrogen stimulates/affects the heat regulating centre of
hypothalamus of brain. Pyrogen changes the set point of heat regulatory centre at a
higher level.

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